Extreme Oncoplasty: Breast Conservation in Patients with Large, Multifocal, and Multicentric Breast Cancer.

INTRODUCTION: Extreme Oncoplastic Breast Conservation Surgery (EOBCS) is offered in selected patients with multifocal or multicentric breast cancer (MFMC). Recent evidence has suggested that EOBCS may be a valuable resource for patients with MFMC who may avoid the risk associated with mastectomy in favour of the benefits of breast conservation without risking their oncological outcomes. Our study examined the practice of EOBCS in two regional breast units in Glasgow, United Kingdom. MATERIALS AND METHODS: A prospectively collected database of 50 patients treated with EOBC in two breast units in Glasgow between 2007 and 2018 were evaluated, and clinical outcomes were observed. RESULTS: Fifty patients (median age 55) underwent EOBCS, of which 43 (86%) had invasive disease. Median tumour size was 55mm (50-90) and multifocal disease was identified in 22 (44%) patients. Nine patients (18%) were found to have positive margins and underwent a second procedure, with 6 (12%) proceeding to mastectomy. Five-year disease free survival rate was 91.5%, while cancer-specific survival was 95.7%. CONCLUSION: EOBCS is oncologically safe in short-term follow-up. Large scale studies are required to confirm these preliminary results, in order to offer EOBCS as a valid option to patients with advanced or multifocal breast cancer.

A prospective cohort study of the safety of breast cancer surgery during COVID-19 pandemic in the West of Scotland.

INTRODUCTION: In order to minimise the risk of breast cancer patients for COVID-19 infection related morbidity and mortality prioritisation of care has utmost importance since the onset of the pandemic. However, COVID-19 related risk in patients undergoing breast cancer surgery has not been studied yet. We evaluated the safety of breast cancer surgery during COVID-19 pandemic in the West of Scotland region. METHODS: A prospective cohort study of patients having breast cancer surgery was carried out in a geographical region during the first eight weeks of the hospital lockdown and outcomes were compared to the regional cancer registry data of pre-COVID-19 patients of the same units (n = 1415). RESULTS: 188 operations were carried out in 179 patients. Tumour size was significantly larger in patients undergoing surgery during hospital lockdown than before (cT3-4: 16.8% vs. 7.4%; p < 0.001; pT2 - pT4: 45.5% vs. 35.6%; p = 0.002). ER negative and HER-2 positive rate was significantly higher during lockdown (ER negative: 41.3% vs. 17%, p < 0.001; HER-2 positive: 23.4% vs. 14.8%; p = 0.004). While breast conservation rate was lower during lockdown (58.6% vs. 65%; p < 0.001), level II oncoplastic conservation was significantly higher in order to reduce mastectomy rate (22.8% vs. 5.6%; p < 0.001). No immediate reconstruction was offered during lockdown. 51.2% had co-morbidity, and 7.8% developed postoperative complications in lockdown. There was no peri-operative COVID-19 infection related morbidity or mortality. CONCLUSION: breast cancer can be safely provided during COVID-19 pandemic in selected patients.

Variation in the management of elderly patients in two neighboring breast units is due to preferences and attitudes of health professionals.

Introduction: Elderly breast cancer patients have been shown to be managed less aggressively than younger patients. There is evidence that their management varies between institutions. We audited the management of elderly patients in two neighboring units in Glasgow and aimed to identify reasons for any differences in practice found. Methods: Patients aged ≥70 years, who were managed for a new diagnosis of breast cancer in the two units between 2009 and 2013, were identified from a prospectively maintained database. Tumor pathology, treatment details, postcode and consultant in charge of care were obtained from the same database. Comorbidities were obtained from each patient's electronic clinical record. Questionnaires were distributed to members of each multidisciplinary teams. Results: 487 elderly patients in Unit 1 and 467 in Unit 2 were identified. 76.2% patients in Unit 1 were managed surgically compared to 63.7% in Unit 2 (p<0.0001). There was no difference between the two units in patient age, tumor pathology, deprivation or comorbidity. 16.2% patients managed surgically in Unit 1 had a comorbidity score of 6 and above compared to 11% of surgically managed patients in Unit 2 (p=0.036). Responses to questionnaires suggested that staff at Unit 1 were more confident of the safety of general anesthetic in elderly patients and were more willing to consider local anesthetic procedures. Conclusion: A higher proportion of patients aged >70 years with breast cancer were managed surgically in Unit 1 compared to Unit 2. Reasons for variation in practice seem to be related to attitudes of medical professionals toward surgery in the elderly, rather than patient or pathological factors.

Oncoplastic breast conservation occupies a niche between standard breast conservation and mastectomy - A population-based prospective audit in Scotland.

INTRODUCTION: The role of oncoplastic breast conservation (OBC) surgery is not fully defined in terms of whether it is equivalent to standard breast conservation (SBC), or more an alternative to mastectomy, or whether it occupies its own niche somewhere between the two. Therefore, we have carried out a population-based prospective audit of the current OBC practice in Scotland. METHODS: All patients diagnosed with breast cancer in the whole of Scotland between 01/01/2014 and 31/12/2015 were prospectively recorded within the National Managed Clinical Networks databases. Patients treated with OBC were compared to patients who had SBC, mastectomy and mastectomy with immediate reconstruction (MIR). RESULTS: 8075 patients were included (OBC:217(2.7%); SBC:5241(64.9%); mastectomy:1907(23.6%); MIR:710(8.8%)). OBC patients were younger than SBC or mastectomy, but older than MIR (p < 0.0001). OBC patients were between SBC and mastectomy patients in terms of clinical and pathological tumour size (all p < 0.001), rates of lobular cancers (v.SBC:p = 0.015 and v.mastectomy:p < 0.001), high-grade tumours (v.SBC:p = 0.030 and v.mastectomy:p = 0.008), ER negative (v.SBC: p = 0.042) and HER-2 positive (v.SBC: p = 0.003) tumours, and nodal metastasis (v.mastectomy: p < 0.001). More OBC patients received (neo)adjuvant chemo- and hormonal therapy (p ≤ 0.001), adjuvant radiotherapy (p = 0.005), trastuzumab (p < 0.001) than SBC. More OBC patients presented through screening (v.mastectomy/MIR: p < 0.0001). Time to surgery from diagnosis was longer for OBC than SBC/mastectomy (p < 0.0001), but shorter than MIR (p = 0.007). CONCLUSION: This national audit demonstrates that OBC occupies its own niche between SBC, mastectomy and MIR in the surgical treatment of breast cancer in Scotland. We recommend that OBC should be recorded separately in other national breast cancer registries.

A population-based audit of surgical practice and outcomes of oncoplastic breast conservations in Scotland - An analysis of 589 patients.

INTRODUCTION: Current evidence for oncoplastic breast conservation (OBC) is based on single institutional series. Therefore, we carried out a population-based audit of OBC practice and outcomes in Scotland. METHODS: A predefined database of patients treated with OBC was completed retrospectively in all breast units practicing OBC in Scotland. RESULTS: 589 patients were included from 11 units. Patients were diagnosed between September 2005 and March 2017. High volume units performed a mean of 19.3 OBCs per year vs. low volume units who did 11.1 (p = 0.012). 23 different surgical techniques were used. High volume units offered a wider range of techniques (8-14) than low volume units (3-6) (p = 0.004). OBC was carried out as a joint operation involving a breast and a plastic surgeon in 389 patients. Immediate contralateral symmetrisation rate was significantly higher when OBC was performed as a joint operation (70.7% vs. not joint operations: 29.8%; p < 0.001). The incomplete excision rate was 10.4% and was significantly higher after surgery for invasive lobular carcinoma (18.9%; p = 0.0292), but was significantly lower after neoadjuvant chemotherapy (3%; p = 0.031). 9.2% of patients developed major complications requiring hospital admission. Overall the complication rate was significantly lower after neoadjuvant chemotherapy (p = 0.035). The 5 year local recurrence rate was 2.7%, which was higher after OBC for DCIS (8.3%) than invasive ductal cancer (1.6%; p = 0.026). 5-year disease-free survival was 91.7%, overall survival was 93.8%, and cancer-specific survival was 96.1%. CONCLUSION: This study demonstrated that measured outcomes of OBC in a population-based multi-centre setting can be comparable to the outcomes of large volume single centre series.

Oncological Outcomes and Complications After Volume Replacement Oncoplastic Breast Conservations-The Glasgow Experience.

INTRODUCTION: Oncoplastic breast conservation surgery (OBCS) combines the principles of surgical oncology and plastic surgery. OBCS has now become a growing option for the treatment of breast cancer and forms a part of breast-conserving therapy (BCT). We sought to investigate and report our experience in two breast units in Glasgow (Victoria Infirmary and Western Infirmary) on volume replacement OBCS. MATERIALS AND METHODS: Details of patients treated with volume replacement OBCS were identified from a prospectively recorded database from November 2010 to October 2015. The clinical records included in the oncoplastic dataset were analyzed for demographics, tumor, treatment characteristics, and recurrences. The data were analyzed for follow-up to determine the pattern and timing of recurrence up to April 2016. The primary outcome of this study was tumor-free margin resection rates, and the secondary outcomes were locoregional and distant recurrence rates as these correlate with the overall oncological safety of volume replacement oncoplastic breast surgery (OPBS). RESULTS: A total of 30 volume replacement oncoplastic breast conservation procedures have been carried out in this time period. The mean age of the former group was 51 years. Twice as many patients presented symptomatically than had tumors detected on screening. The mean preoperative tumor size on radiology was 25.4 mm. Patients underwent 13 thoracoepigastric flaps, 5 lateral intercostal artery perforator (LICAP) flaps, 2 thoracodorsal artery perforator (TDAP) flaps, 1 lateral thoracic artery perforator (LTAP) flap, 1 crescent flap volume replacement surgery, and 8 matrix rotations. Two patients had neoadjuvant chemotherapy. Fourteen patients had adjuvant chemotherapy, and all patients were treated with adjuvant radiotherapy. Twenty-two patients were treated with hormonal therapy and four patients were treated with Herceptin. The rate of incomplete excision was 10%. Median follow-up time was 48.5 months. Only one regional recurrence was detected. Eight patients encountered some form of complication. CONCLUSION: This study continues to show the relative oncological safety of volume replacement oncoplastic conservations as an option for reconstruction in breast cancer patients. Further research is urgently needed to build robust evidence supporting the long-term oncological safety.

Six-year follow-up of patients treated with oncoplastic reduction mammoplasty: A cohort study.

BACKGROUND: Current evidence for the oncological safety of oncoplastic breast conservation is poor as it is based mostly on short-term follow-up data. Hence, we report long-term recurrence rates in patients treated with oncoplastic reduction mammoplasty (ORM). METHODS: A prospectively maintained database was searched to identify patients who underwent ORM between 2005 and 2010. A retrospective review of medical records was carried out, including patients with ductal carcinoma in situ and invasive breast cancer. RESULTS: Follow-up data from 65 consecutive patients with ORM were reviewed, of which 50 patients were eligible to measure long-term recurrence rates. The average weight of the resected tissue was 272 g altogether. The mean preoperative tumour size was 2.95 cm on imaging. 64% of patients had stage II - III cancers. Incomplete excision rate after ORM was 16.1%, completion mastectomy rate was 10.7%. During a median follow-up of 72 months, 2% local, 6% distant recurrence rates were detected. The breast cancer-specific survival rate was 96% per cent. CONCLUSIONS: Based on these long-term follow-up data, ORM is an oncologically safe treatment option.

Imaging Results Following Oncoplastic and Standard Breast Conserving Surgery.

BACKGROUND: Oncoplastic breast-conserving surgery (OBCS) requires more complex surgical techniques than standard wide local excision (WLE) and the postoperative complication rate may be higher. Since these can have an impact on postoperative imaging, we compared imaging and biopsy results after OBCS and WLE. METHODS: Findings for patients undergoing OBCS (n = 83) or standard WLE (n = 128) were compared. Numbers, indications and outcomes of mammograms, breast ultrasounds, magnetic resonance imaging scans and biopsies done within 2 years after surgery were analysed. RESULTS: OBCS was applied for more advanced malignancy. Significantly more patients required breast ultrasound after OBCS than WLE (20/71 vs. 17/116; p = 0.024). Breast Imaging Reporting and Data System (BI-RADS) category 3 or 4 ultrasound results were found only in patients with OBCS (6/29 vs. 0/19; p = 0.034). Significantly more biopsies were required after OBCS (9/71 vs. 3/116; p = 0.006). New lumps or lumpiness were the commonest indications, and pathology confirmed fat necrosis in the majority (7/12). The rate of fat necrosis after OBCS was 18% on clinical examination (13/71), 15% with ultrasound (11/71) and 7% confirmed on pathology (5/71). CONCLUSION: Patients treated with OBCS require significantly more ultrasound scans and consequent biopsies than patients who underwent WLE. This is mainly due to fat necrosis developing after OBCS in the majority of cases.

Optimum duration of neoadjuvant letrozole to permit breast conserving surgery.

The aim of this multicenter, prospective, longitudinal phase IV study was to establish the optimal duration of neoadjuvant letrozole that would allow breast conservation surgery (BCS) in patients with early breast cancer who were initially unsuitable. Primary, invasive, estrogen-receptor- and/or progesterone-receptor-positive breast cancer patients, with large tumors (≥T2 i.e., >20 mm) not initially suitable for BCS, received 2.5 mg letrozole p.o. daily. Patients continued treatment until they became eligible for BCS, progressed, failed to meet criteria for BCS and withdrew for scheduled mastectomy, withdrew for other reasons, or completed 12 months of letrozole treatment without a BCS decision being made. A total of 146 patients were enrolled; seven patients who did not have a valid postbaseline tumor assessment were excluded from the final efficacy analysis. At study closure, 69 % of patients (96 of 139) were eligible for BCS. The median time to achieve a tumor response sufficient to allow BCS with neoadjuvant letrozole was 7.5 months (95 % CI 6.3-8.5 months). Letrozole was well tolerated, and most adverse events were mild-to-moderate (grade 1-2). The results from this trial suggest that extended letrozole therapy in the neoadjuvant setting (7.5 months), as opposed to conventional treatment of 4 months, is optimal to achieve maximum reduction in tumor volume sufficient for BCS.

The relationship between lymphovascular invasion and angiogenesis, hormone receptors, cell proliferation and survival in patients with primary operable invasive ductal breast cancer.

BACKGROUND: Several well-established tumour prognostic factors are used to guide the clinical management of patients with breast cancer. Lymphovascular invasion and angiogenesis have also been reported to have some promise as prognostic factors. The aim of the present study was to examine the prognostic value of tumour lymphovascular invasion and microvessel density compared with that of established prognostic factors in invasive ductal breast cancer. METHODS: In addition to hormone receptor status and Ki-67 proliferative activity, lymphovascular invasion and microvessel density and their relationship with survival were examined in patients with invasive ductal breast cancer. Full sections and tissue microarrays (n = 384 patients) were utilised to assess these factors and were scored by appropriate methods. RESULTS: On univariate analysis tumour size (P < 0.05), lymph node involvement (P < 0.01), lymphovascular invasion (P < 0.05), microvessel density (P < 0.05) and local- regional treatment (P < 0.01) were associated with poorer survival in ER negative tumours. On multivariate analysis in ER negative tumours lymph node involvement (P < 0.01) and local- regional treatment (P < 0.05) were independently associated with poorer cancer-specific survival. On univariate analysis tumour grade (P < 0.05), lymph node involvement (P < 0.001), HER-2 (P < 0.05), Ki-67 (P < 0.01) and lymphovascular invasion (P < 0.001) were associated with poorer survival in ER positive tumours. On multivariate analysis lymph node involvement (P < 0.001), Ki-67 (P < 0.001) and lymphovascular invasion (P < 0.05) were independently associated with poorer cancer-specific survival in ER positive tumours. CONCLUSION: Lymphovascular invasion but not microvessel density was independently associated with poorer survival in patients with ER positive but not ER negative invasive ductal breast cancer.

Comparison of visual and automated assessment of microvessel density and their impact on outcome in primary operable invasive ductal breast cancer.

Angiogenesis is essential for tumor growth and metastasis, and several studies have reported increased angiogenesis, as quantified by microvessel density, to be a powerful prognostic tool in breast cancer. Therefore, there is considerable interest in automated assessment of microvessel density with possible benefits in improved accuracy, increased precision, and handling workload. Visual and automated assessment of microvessel density (CD34(+)) and survival were examined in patients with primary operable invasive ductal breast cancer. Tissue microarrays (n = 356 patients) immunostained for microvessel density (CD34(+)) were scored visually and automatically with the Slidepath Tissue IA system (Dublin, Ireland). Visual and automated microvessel density (CD34(+)) were in agreement (interclass correlation coefficient = 0.69, P < .001). Visual but not the automated method for microvessel density (CD34(+)) was associated with locoregional treatment and metastasis. On univariate survival analysis, visual but not automated method for microvessel density (CD34(+)) was associated with recurrence-free and cancer-specific survival in patients with invasive ductal breast cancer (P < .01). Although automated assessment of microvessel density (CD34(+)) is in reasonable agreement, it poorly predicts outcome in patients with operable invasive ductal breast cancer.

Interactions between MAP kinase and oestrogen receptor in human breast cancer.

PURPOSE: The oestrogen receptor (ERα) may be activated in a ligand-dependent manner, via oestrogen, or in a ligand-independent manner, via signal transduction pathways. Mitogen Activated Protein Kinase (MAPK) is known to directly phosphorylate ERα at serine 118 in a ligand-independent manner. This study investigated the interaction between MAPK and ERα in breast cancer. MATERIALS & METHODS: Immunohistochemical experiments were undertaken to determine the expression of MAPK, pMAPK and pER(ser118) in breast tumours to determine their clinical relevance. Immunofluorescent experiments were performed, on MCF-7 breast cancer cells, to monitor the phosphorylation and localisation of MAPK and ERα in response to oestrogen, heregulin and a MAPK inhibitor. RESULTS: Oestrogen and Heregulin stimulated phosphorylation of ERα and its nuclear translocation, but heregulin induced this at levels much lower than those observed with oestrogen. Following stimulation with heregulin, but not oestrogen, treatment with MAPK inhibitor reduced the levels of nuclear pER(ser118). In cells treated with both oestrogen and heregulin, nuclear pER(ser118) was visible; but at levels comparable with heregulin treatment alone. CONCLUSION: This study confirms that ligand-mediated phosphorylation is associated with rapid nuclear localisation of ERα, due to oestrogen binding. ERα is phosphorylated at serine 118 in a ligand-independent manner. Preventing nuclear translocation of pMAPK reduced the levels of ligand-independent, but not ligand-dependent phosphorylation of ERα. Co-stimulation with both oestrogen and heregulin suggested that heregulin mediated signalling determines the subcellular localisation of ERα. Activation of ERα by direct phosphorylation may result in its rapid deactivation due to degradation or nuclear export.

Comparison of visual and automated assessment of HER2 status and their impact on outcome in primary operable invasive ductal breast cancer.

AIMS: To compare visual and computerized image analysis of HER2 immunohistochemistry (IHC) with fluorescence in-situ hybridization (FISH) for HER2 status, and to examine the relationships with outcome in patients with primary operable invasive ductal breast cancer. METHODS AND RESULTS: Tissue microarrays for 431 breast cancer patients were used to compare different approaches to the assessment of HER2 status. The cores were scored visually and with the Slidepath Tissue IA system, using the NICE-approved scoring system for the HercepTest, as well as by FISH. The agreement between visual and image analysis of HER2 IHC was excellent [interclass correlation coefficient (ICCC) = 0.95, rs = 0.90, r = 0.91, k = 0.81, and P < 0.001]. The agreement of HER2 FISH with visual and image analysis of HER2 IHC was also excellent (ICCC = 0.95 and ICCC = 0.92, respectively). Univariate survival analysis showed equivalent associations of visual and image analysis of HER2 and HER2 FISH with both recurrence-free survival (all P < 0.01) and cancer-specific survival (all P < 0.05) in patients with invasive ductal breast cancer. CONCLUSION: Computerized image analysis of HER2 IHC gives results comparable to those obtained with visual assessment, with possible advantages in diagnostic pathology.

Breast cancer outcomes by steroid hormone receptor status assessed visually and by computer image analysis.

AIMS: To compare the assessment of steroid hormone receptor immunohistochemistry by eye and by computer-aided image analysis, and to examine their relationships with survival in breast cancer. METHODS AND RESULTS: Allred scores and weighted histoscores for oestrogen receptor (ER) and progesterone receptor (PR) immunohistochemistry were determined by eye (visual histoscore) for 459 primary invasive ductal breast carcinomas in triplicate tissue microarrays. Histoscores were also determined by computerized image analysis (automated histoscore). ER and PR status determined by these different methods were compared with each other and in their ability to predict survival over at least 142 months of follow-up. Allred and visual histoscore were highly associated for ER and PR (both P < 0.001). By univariate analysis, Allred score and visual histoscore for ER and PR were highly associated with recurrence-free and cancer-specific survival (both P < 0.001) in patients with invasive ductal breast cancer overall, in those who received tamoxifen, and in those with recurrence on tamoxifen. Visual and automated histoscores were in excellent agreement for ER and PR (both P < 0.001), and were equally effective in predicting recurrence and survival for patients with invasive breast cancer who received tamoxifen. CONCLUSIONS: Automated histoscore appears to be a valid alternative to visual histoscore or Allred score for determining ER and PR status.

When to start an aromatase inhibitor: now or later?

Among women who have undergone surgery for breast cancer, the risk of recurrence, especially distant metastases, peaks 1-2 years postsurgery. Recent clinical trial evidence suggests that initial adjuvant therapy with an aromatase inhibitor (AI) can reduce this early risk of recurrence. According to the recently updated St Gallen consensus statement, initial AI therapy is the preferred strategy for adjuvant endocrine therapy in postmenopausal women with hormone receptor-positive breast cancer.

Use of aromatase inhibitors and bisphosphonates as an anticancer therapy in postmenopausal breast cancer.

Breast cancer is a major cause of morbidity and mortality in postmenopausal women worldwide. Reducing the risk of distant disease recurrence is a primary goal of adjuvant endocrine therapy. As we await data from ongoing Phase III comparison trials, an emerging body of evidence demonstrates important differences between third-generation aromatase inhibitors, particularly with respect to potency and prevention of early distant metastases. Furthermore, a growing body of evidence demonstrates anticancer benefits of bisphosphonates in adjuvant breast cancer and other settings. This article outlines the proceedings from an Expert Panel meeting of regionally diverse breast cancer specialists regarding the appropriate use of aromatase inhibitors in postmenopausal hormone-responsive early breast cancer and bisphosphonates as anticancer therapy in adjuvant breast cancer.

Osteoclast-like giant cell tumor arising in the soft tissue of the breast: report of a case.

Extraosseous manifestations of osteoclast-like giant cell tumors (OGCTs) in soft tissue are unusual, especially in the breast. However, multinucleated osteoclast-like giant cells have been described in association with epithelial malignancy, as a variant of breast carcinoma. We report a case of OGCT of the soft tissue of the breast, not associated with epithelial elements. To the best of our knowledge, this is only the second such case reported.

Patterns and predictors of early recurrence in postmenopausal women with estrogen receptor-positive early breast cancer.

Previous studies suggest that disease recurrence peaks at around 2 years in patients with early stage breast cancer (EBC), but provide no data regarding recurrence type. This retrospective analysis aimed to identify early recurrence types and risk factors in estrogen receptor-positive (ER+) EBC patients treated with adjuvant tamoxifen following breast cancer surgery. Postmenopausal women diagnosed with ER+ EBC from 1995 to 2004 were evaluated. Annual hazard ratios (HR) for recurrence at different sites were calculated. Time-dependent Cox regression analysis was used to identify predictors of recurrence within 2.5 years of diagnosis, including factors that were more strongly predictive of early than later recurrence. Of 3,614 patients evaluated, 476 developed recurrence during the 5-year median follow-up. Cumulative recurrence rates at 2.5 years (95% confidence interval) were: overall 6.3% (5.5-7.1), locoregional 1.1% (0.7-1.5), contralateral 0.5% (0.3-0.7), and distant 4.8% (4.0-5.6). The annual HR of overall recurrence peaked at 2 years (4.3% per annum). The majority of this peak represented distant recurrence (3.4% per annum). In Cox regression analysis, tumor size and grade, lymph node involvement, lymphovascular invasion, and symptomatic presentation were significant independent predictors of early recurrence. Age at diagnosis was independently predictive of recurrence within 2.5 years of diagnosis but not later recurrence. This study identified an early recurrence peak at 2 years, most of which were distant recurrences. Implementing an aromatase inhibitor after an initial 2-3 years of tamoxifen fails to address this early peak of distant recurrence and the potential breast cancer-associated mortality.